An estimated one in five couples in the United States has some degree of infertility. Infertility is defined as the inability of a heterosexual couple to achieve a pregnancy within one year of unprotected intercourse (Cecil Textbook of Medicine, W. B. Saunders Company, 19th Ed., p. 1339-1340, (1992)). Major etiological factors include ovulatory dysfunction, abnormal tubal function, cervical factors, and male sperm factors. (The Merck Manual of Diagnosis and Therapy, Merck Research Laboratories, 16th Ed., p. 1768-1770, (1992)). An estimated five to six percent of men in the reproductive age group are infertile. Most causes of male infertility are due to an abnormal sperm count or low semen quality.
A majority of problems associated with fertility in males stem from changes in testosterone levels. In particular, decreases in concentration of this steroid can result in infertility and impotence. Endogenous estrogen has been well-documented to serve as a regulatory factor in testosterone production by interaction with the estrogen receptor (Nozu, K. et al., J. Biol. Chem. 256, 1915 (1981); Brinkman, A. et al., Endocrinology, 110, 1834 (1982)). Thus, intratesticular estrogen plays a key role in testosterone steroidogenisis with increased levels of estrogen inhibiting testosterone production (Cigorraga, S. B. et al., J. Clin. Invest. 65, 699 (1982); Padron, R. S. J., Clin. Endocrinol. Metab. 50, 1100 (1980)). A need exists for new methods of treating or preventing male infertility.